INFLAMMATORY ROLES OF P-SELECTIN
INFLAMMATORY ROLES OF P-SELECTIN
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DOI：
10.1172/jci116623
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发表时间：
1993-08-01
影响因子：
15.9
通讯作者：
ZIMMERMAN，GA
中科院分区：
文献类型：
--
作者：
LORANT，DE;TOPHAM，MK;ZIMMERMAN，GA
多形核白细胞（PMNs）快速可逆地与诱导表达P-选择素的内皮细胞结合，P-选择素是一种介导粘附性细胞间相互作用的糖蛋白。此外，粘附于表达P-选择素的内皮的PMN表现出细胞内Ca 2+瞬变，功能性上调β-2-整合素（CD 11/CD 18糖蛋白），形状极化，并且当随后用趋化因子刺激时引发增强的脱粒。然而，当单独使用、掺入模型膜或由转染细胞表达时，P-选择素不会直接诱导这些反应。没有直接激活的PMN是由于竞争的P-选择素的抑制作用，相反，纯化的P-选择素和P-选择素的膜支持激动剂刺激的PMN反应。此外，如阻断单克隆抗体的实验所示，需要P-选择素将PMN拴系到内皮表面以有效地引发。启动事件直接由信号分子血小板活化因子（PAF）介导，并通过阻断PMN上的PAF受体而被抑制。因此，P-选择素和PAF是粘附和激活级联反应的组分，但具有不同的作用：P-选择素束缚并捕获PMN，而PAF介导阿曲他克林激活。在体内，除了介导白细胞的滚动和其他粘附功能外，选择素还可以促进靶细胞与发送细胞间信号的膜结合分子的相互作用。图片
Polymorphonuclear leukocytes (PMNs) bind rapidly and reversibly to endothelial cells induced to express P-selectin, a glycoprotein that mediates adhesive intercellular interactions. In addition, PMNs adherent to endothelium expressing P-selectin demonstrate an intracellular Ca2+ transient, functionally up-regulate beta-2-integrins (CD11/CD18 glycoproteins), become polarized in shape, and are primed for enhanced degranulation when subsequently stimulated with chemotactic factors. However, P-selectin induces none of these responses directly when used alone, when incorporated into model membranes, or when expressed by transfected cells. The absence of direct activation of the PMNs is not due to competing antiinflammatory effects of P-selectin; instead, purified P-selectin and P-selectin in membranes support agonist-stimulated PMN responses. Furthermore, tethering of PMNs to endothelial surfaces by P-selectin is required for priming to occur efficiently, as shown by experiments with blocking monoclonal antibodies. The priming event is directly mediated by the signaling molecule, platelet-activating factor (PAF), and is inhibited by blocking the PAF receptor on PMNs. Thus, P-selectin and PAF are components of an adhesion and activation cascade, but have distinct roles: P-selectin tethers and captures the PMN, whereas PAF mediates juxtacrine activation. In vivo, selectins may facilitate interaction of target cells with membrane-bound molecules that send intercellular signals, in addition to mediating rolling of leukocytes and other adhesive functions.Images